The integrated function of dopaminergic, GABAergic and substance P neurons was investigated in striatum and N. accumbens after short- and long-term treatment with antischizophrenic drugs. The data suggest that GABA and substance P terminals in SN may be involved in mediating the effect of antischizophrenic drugs on nigro-striatal DA system. Long-term treatment with classical (cataleptogenic) antischizophrenic drugs produces tolerance to the activation of the DA striatal system. Tolerance is not observed after long-term treatment with atypical (non-cataleptogenic) antischizophrenic drugs. In striatum the supersensitivity of DA receptors produced by these drugs is associated with an increase in calcium binding protein (calmodulin). These data suggest that the DA neurons adapt to the effect elicited by antischizophrenic drugs when supersensitivity of DA receptors develops.